Pyruvate Dehydrogenase E1-alpha subunit: Proteins and Enzymes

Pyruvate Dehydrogenase E1-alpha subunit (PDHE1 alpha) is a member of the pyruvate dehydrogenase complex (PDC) and is a nuclear-encoded mitochondrial matrix multienzyme complex that provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the irreversible conversion of pyruvate into acetyl-CoA. The PDH complex is composed of multiple copies of 3 enzymes: E1 (PDHA1 or PDHE1), dihydrolipoyl transacetylase (DLAT), and dihydrolipoyl dehydrogenase (DLD). The E1 enzyme is a heterotetramer of 2 alpha and 2 beta subunits. The E1-alpha subunit contains the E1 active site and plays a key role in the function of the PDH complex. Enhanced expression of pyruvate dehydrogenase kinase-1 (PDK-1) results in phosphorylation of PDHE1 alpha at Serine 293, which in turn produces nearly complete inhibition of the pyruvate dehydrogenase complex (PDC). A recent study shows that inhibition of PDC activity in cancer cells restores normoxic stablization of HIF-1 alpha by glycolytic metabolites.